Vol 61: january • janVier 2015
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Canadian Family Physician•Le Médecin de famille canadien41
Polyunsaturated fatty acids and fetal brain development
Unfulfilled promises
Gideon Koren
MD FRCPC FACMTMotherisk Update
Abstract
Question I have learned that one of the manufacturers of prenatal vitamins has added omega-3 fatty acids and claims that they help support fetal cognitive health and brain function. Is this based on evidence?
Answer The claim that polyunsaturated fatty acids help improve fetal brain and eye development has been made for more than a decade. Unfortunately it is not supported by evidence-based science. Long-term studies have failed to show such effects. Implying to women that using these products will improve the brain development of their children is unwarranted and misleading. Health Canada should clarify the contradictions in its statements about omega-3 fatty acids.
Acides gras polyinsaturés et développement du cerveau fœtal
Promesses brisées Résumé
Question J’ai appris que l’un des fabricants de vitamines prénatales y a ajouté des acides gras oméga-3 et prétend qu’ils aident à maintenir la santé cognitive et la fonction cérébrale du fœtus. Cette affirmation se fonde-t-elle sur des données probantes?
Réponse L’affirmation que les acides gras polyinsaturés aident à améliorer le développement du cerveau et des yeux du fœtus existe depuis plus d’une décennie. Malheureusement, elle n’est pas étayée par la science fondée sur des données probantes. Des études à long terme n’ont pas réussi à démontrer de tels effets.
L’insinuation voulant que les femmes qui utilisent ces produits amélioreront le développement cérébral de leurs enfants est injustifiée et trompeuse. Santé Canada devrait clarifier les contradictions qui existent dans les déclarations qu’a faites le ministère à propos des acides gras oméga-3.
P
olyunsaturated fatty acids (PUFAs) of the omega-3 and omega-6 families are not synthesized by the human body,1 making the parent fatty acids of these families—α-linolenic acid and linoleic acid—essential fatty acids that must be obtained through the diet.2 The ratio of omega-3 to omega-6 PUFAs is critical because both families are metabolized by the same enzymes, and increasing the amount of omega-3 fatty acids in the diet, for example, might decrease the availability of the omega-6 fatty acids. Because the PUFAs required by the fetus are supplied by preferential placental transfer of long-chain PUFAs rather than the precursors α-linolenic acid and linoleic acid, it has been proposed that an addi- tional maternal supply of docosahexaenoic acid (DHA) and arachidonic acid during pregnancy might improve early cognitive and visual development.3 Observational studies have suggested that prenatal arachidonic acidstatus correlates positively with neurodevelopmental outcomes during early infancy, but not at older ages.4
Limited benefit
In the Health Canada document Fish and Omega-3 Fatty Acids,5 women are advised to consume at least 150 g of cooked fish weekly. With respect to PUFA supple- mentation with fish oil, although such supplements provide omega-3 fatty acids, Health Canada stated that there is insufficient evidence to draw conclusions on the effects of fish oil supplementation on infant devel- opment.5 Motherisk addressed this question in a recent systematic review of the potential effects of interven- tional supplementation of omega-3 fatty acids during pregnancy only on infant neurobehavioural and visual development, without the potential effects of breast- feeding or later dietary supplementation.6 Nine studies
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Canadian Family Physician•Le Médecin de famille canadien|
Vol 61: january • janVier 2015Motherisk Update
met the inclusion criteria, 3 focusing on development of vision and 6 on neurobehavioural development.
Synthesizing the existing data, most studies did not show sustained benefits to infant cognition or devel- opment of vision. Since the publication of this system- atic review, a study published in May 2014 in JAMA also could not confirm a beneficial effect in a randomized trial of children aged 4 years.7
The randomized trials we reviewed focused on the effects of maternal PUFA supplementation on the neu- rocognitive and retinal development in the child; they found very limited, if any, benefits to supplementation.
Even in the studies that found statistically significant differences between the treatment and control groups, the differences were small and of little potential clinical importance. These trials found that even high doses of omega-3 PUFAs0 (up to 3.7 g per day) were not associ- ated with any detrimental effects.6
In the longitudinal studies by Helland et al, the lim- ited effects evident at 4 years of age were nullified 3 years later.8-10 In the study by Dunstan et al, a single pos- itive effect was contrasted by mostly negative results.11 When comparing numerous end points, a single positive result might arise by chance only, as P < .05 means a 1 in 20 chance of “no difference” becoming “a significant difference,” especially as multiple comparison correc- tion for the large number of comparisons was not per- formed in the study by Dunstan et al.11 Similarly, Judge et al found 1 significantly positive effect in a large num- ber of negative tests (P < .05).12 If there was a genuine favourable effect, it was of small magnitude and might not have persisted in later years. Thus, in considering the results of these studies, a recommendation to sup- plement all expecting mothers with PUFAs to improve infant neurodevelopment is not currently supported by the existing data.
Recent developments
In the study published in May 2014, Makrides and col- leagues conducted a 4-year follow-up of children born to women participating in a randomized trial of prena- tal DHA supplementation. Their data indicate that such supplementation “does not influence objective assess- ments of cognition, language, and executive function.“7
Unfortunately, in a monograph on fish oil dated July 10, 2013, Health Canada states:
For products providing 100-5,000 mg EPA [eicosapentae- noic acid] + DHA including at least 100 mg DHA, per day:
Helps support cognitive health and/or brain function.13
For products providing 150-2,000 mg EPA + DHA including at least 150 mg DHA, per day ... Helps sup- port the development of the brain, eyes and nerves in children up to 12 years of age.13
These statements contradict previous Health Canada statements,5 and overwrite the statement by Makrides and colleagues quoted above that PUFAs were not shown to confer such effects.7
Conclusion
These incorrect and misleading statements are used inap- propriately by manufacturers to declare benefits that are not supported by science. Implying to women that using these products will improve brain development of their children is unwarranted and misleading. Health Canada should clarify the ambiguity that exists in its statements.
Competing interests None declared references
1. Dubnov-Raz G, Finkelstein Y, Koren G. ω-3 fatty acid supplementation during pregnancy. For mother, baby, or neither? Can Fam Physician 2007;53:817-8.
2. Koletzko B, Lien E, Agostoni C, Böhles H, Campoy C, Cetin I, et al. The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy:
review of current knowledge and consensus recommendations. J Perinat Med 2008;36(1):5-14.
3. Szajewska H, Horvath A, Koletzko B. Effect of n-3 long-chain polyunsatu- rated fatty acid supplementation of women with low-risk pregnancies on pregnancy outcomes and growth measures at birth: a meta-analysis of ran- domized controlled trials. Am J Clin Nutr 2006;83(6):1337-44.
4. Hadders-Algra M. Prenatal long-chain polyunsaturated fatty acid status: the importance of a balanced intake of docosahexaenoic acid and arachidonic acid. J Perinat Med 2008;36(2):101-9.
5. Health Canada. Prenatal nutrition guidelines for health professionals. Fish and omega-3 fatty acids. Ottawa, ON: Health Canada; 2009.
6. Lo A, Sienna J, Mamak E, Djokanovic N, Westall C, Koren G. The effects of maternal supplementation of polyunsaturated fatty acids on visual, neurobehavioural, and developmental outcomes of the child: a system- atic review of the randomized trials. Obstet Gynecol Int 2012;2012:591531.
DOI:10.1155/2012/591531. Epub 2012 Jan 18.
7. Makrides M, Gould JF, Gawlik NR, Yelland LN, Smithers LG, Anderson PJ, et al. Four-year follow-up of children born to women in a randomized trial of prenatal DHA supplementation. JAMA 2014;311(17):1802-4.
8. Helland IB, Saugstad OD, Smith L, Saarem K, Solvoll K, Ganes T, et al.
Similar effects on infants of n-3 and n-6 fatty acids supplementation to preg- nant and lactating women. Pediatrics 2001;108(5):E82.
9. Helland IB, Smith L, Blomén B, Saarem K, Saugstad OD, Drevon CA. Effect of supplementing pregnant and lactating mothers with n-3 very-long-chain fatty acids on children’s IQ and body mass index at 7 years of age. Pediatrics 2008;122(2):e472-9.
10. Helland IB, Smith L, Saarem K, Saugstad OD, Drevon CA. Maternal supple- mentation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children’s IQ at 4 years of age. Pediatrics 2003;111(1):e39-44.
11. Dunstan JA, Simmer K, Dixon G, Prescott SL. Cognitive assessment of chil- dren at age 2(1/2) years after maternal fish oil supplementation in pregnancy:
a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2008;93(1):
F45-50. Epub 2006 Dec 21.
12. Judge MP, Harel O, Lammi-Keefe CJ. Maternal consumption of a docosa- hexaenoic acid-containing functional food during pregnancy: benefit for infant performance on problem-solving but not on recognition memory tasks at age 9 mo. Am J Clin Nutr 2007;85(6):1572-7.
13. Health Canada. Fish oil [monograph]. Ottawa, On: Health Canada; 2013.
Motherisk questions are prepared
by the Motherisk Team at the Hospital for Sick Children in Toronto, Ont. Dr Koren is Director of the Motherisk Program. Dr Koren is supported by the Research Leadership for Better Pharmacotherapy during Pregnancy and Lactation.
Do you have questions about the effects of drugs, chemicals, radiation, or infections in women who are pregnant or breastfeeding? We invite you to submit them to the Motherisk Program by fax at 416 813-7562; they will be addressed in future Motherisk Updates. Published Motherisk Updates are available on the Canadian Family Physician website (www.cfp.ca) and also on the Motherisk website (www.motherisk.org).
